Documentation has taught us that the materials used for the purposes of implantation in the human body may be of different types.
There are biotolerant materials, bioinert materials and bioactive materials of which some examples appear in Table 1 established by Kienapfel H., Sprey C., Wilke A., Griss P., Implant fixation by bone ingrowth, The Journal of Arthroplasty, Volume 14 No. 3, 1999, which Table 1 also sets out the level of biocompatibility of some of the materials examined in contact with the bone. The distinction between these types of materials is the manner in which they will be accepted by the organism. In this manner, the biotolerant materials will be encapsulated by a fibrous material. Bioinert materials will not bring about a reaction of the living tissues. The bone will be able to grow on these materials without a chemical bond. Conversely, the bioactive materials will integrate excellently in the living environment by creating chemical bonds therewith.
TABLE 1Extent of theMaterialsbiocompatibilityOsteogenesisPMMA (PolymethylBiotolerantRemote osteogenesismethacrylate)Stainless steelBiotolerantRemote osteogenesisAluminaBioinertContactosteogenesisCarbonBioinertContactosteogenesisTitanium andBioinertContacttitanium-basedosteogenesisalloysChromium/cobaltBioinertOsteogenesis withalloysbondPhosphocalcicBioactiveOsteogenesis withceramicsbond
Kokubo T. (see “Bioactive glass ceramics: properties and applications, Biomaterials 12, pages 155-163, 1991” and see also “Formation of biologically active bone-like apatite on metals and polymers by a biomimetic process, Thermochimica Acta 280/281, pages 479-490, 1996”) has carried out research concluding that the connection between the titanium and the bone is carried out by means of a film of apatite, in particular in the form of hydroxyapatite which is a mineral species of the phosphate family, having the formula Ca5(PO4)3(OH). It is known that titanium is bioinert. The bone can therefore not bond chemically thereto. However, it has been found that, following an implant of titanium, the biological fluids deposit on the implant a film of calcium phosphate which will chemically bond to the titanium of the implant, and it is to this deposit, in which the levels of calcium and phosphorus are in the ratio Ca/P of approximately from 1.57 to 1.62 and whose constitution is therefore very close to that of the human bone, that the bone can chemically bond.
FIG. 1 further shows the method for attaching the bone to an implant in vivo.
To this end, scientists have developed techniques for evaluation of the bioactivity using for this purpose solutions which simulate the mineral portion of human blood plasma and which therefore contain the same ions as the blood plasma, and at equivalent concentrations. Several solutions of this type, referred to as “Simulated Body Fluid” or SBF, have been disclosed over recent years. After the first SBF created by Kokubo in 1991, improvements were made to this fluid so that it represents the mineral portion of the human blood plasma to the greatest possible extent. The chemical properties of the SBF thus allow the bioactivity of a material to be evaluated by immersing it in the SBF fluid for a length of time and observing the surface thereof after drying.
Table 2, communicated by Kokubo T., Takadama H. (How useful is SBF in predicting in vivo bone bioactivity, Biomaterials 27, pages 2907-2915, 2006), further establishes the comparison between the composition of human blood plasma and different SBFs.
TABLE 2Ionic concentration (mM)Na+K+Mg2+Ca2+Cl−HCO3−HPO42−SO42−Human142.05.01.52.5103.027.01.00.5bloodplasmaStarting142.05.01.52.5148.84.21.00SBFCorrected142.05.01.52.5147.84.21.00.5SBF (c-SBF)Revised142.05.01.52.5103.027.01.00.5SBF (r-SBF)Resulting142.05.01.52.5103.04.21.00.5improvedSBF
According to Kokubo, the layer which is indispensable for the connection between the bone and the titanium in vivo can be reproduced in vitro by immersion in the SBF. The capacity of a material to create bonds with the bone corresponds to the capacity thereof to be covered with a layer of apatite when it is immersed in this bodily fluid simulated in vitro. Conversely, the bone colonisation will not be able to be carried out on a material which does not have a deposit of apatite after it has been immersed in the SBF.
The observation of the deposit of apatite can be carried out by means of electronic microscopy and the analysis of the composition of this deposit can be carried out using any chemical analysis method.
Still according to Kokubo, it is consequently possible to compare the bioactivity of several materials by comparing the deposition speed of the apatite on these different materials when they are immersed in SBF.
In 2008, concentrating more specifically on pure titanium, the team of Waléria Silva de Meideros, de Oliveira M. V., Pereira L. C. and Andrade M. C. (Bioactive Porous Titanium: an alternative to surgical implants, Artificial Organs 32(4), pages 277-282, 2008) immersed in SBF porous samples of pure titanium. This team has concluded that, after seven days, a deposit of calcium could be identified. Then, after fourteen days, it was possible for them to observe by means of EDX analysis the presence of calcium and phosphorus. Furthermore, as shown in FIG. 2, it can be seen that after fourteen and twenty-eight days of immersion, respectively, a film of calcium phosphate is present at the surface of the material.
According to Kokubo, in his article mentioned above which appeared in 1996 in “Thermochimica Acta”, the layer of apatite which is deposited on the material implanted in the human body is carried out using hydroxyl groups (OH) present on the surface of the material. These hydroxyl groups appear as a result of the action of the biological fluids on the material. A layer containing hydrated titanium oxides (HTiO3—) may be reproduced, for titanium, by immersing it in a solution which contains sodium hydroxide NaOH concentrated at 10 moles per liter. This is because the immersion of the titanium in this solution allows the passive layer of oxide to be dissolved at the surface and a new layer of oxides to be created which are necessary for the attachment of the layer of apatite. The same author informs us that this new layer of oxides is unstable both mechanically and chemically. In order to stabilise it, he carries out a thermal processing operation at 600° C. in order to render this deposit amorphous and crystalline. The presence of this layer facilitates the appearance, at the surface of the material, of hydroxyl groups (TiOH) which will bring about the formation of apatite.
Lenka Jonasova and his team (Jonasova L., üller F. A., Helebrant A., Strnad J., Greil P., Biomimetic apatite formation on chemically treated titanium, Biomaterials 25, pages 1187-1194, 2004) have worked on this same subject-matter. However, for their part, they have sought to improve such a method for processing titanium with sodium hydroxide by preparing the titanium beforehand and, more specifically, by pickling it with a solution containing HCl. According to their work, this prior preparation allows, before the processing with NaOH, a layer of TiO2 to be obtained which is finer and more uniform than without such a pickling operation. Samples which had been processed using this method (HCl, then NaOH) were then immersed in SBF. Following each step, chemical analyses were carried out and suppositions relating to the chemical reactions which had taken place, leading to modifications of the surface of the samples of titanium, were transmitted as can be seen in FIG. 7.
It appears that the pickling is successful in degrading the layer of TiO2 naturally present on the surface of the titanium and that, following this degradation, a layer of TiH2 is formed. In contact with ambient air, a new layer of TiO2 which is finer is formed. The immersion in sodium hydroxide NaOH allows this surface layer of TiO2 to be dissolved and a new titanium oxide which contains Na+ ions to be formed. During the immersion in the SBF, an exchange of ions is produced between this and the surface of the titanium. This leads to the formation of a layer of TiOH. The Ca2+ ions are then incorporated into this layer and it is these Ca2+ ions which, owing to their positive charge, will allow apatite to be formed on the surface. This is because the ions (PO4)3− and (CO3)2− will be able to become attached thereto and thus form apatite. The apatite formed in this instance at the surface is HydroxyCarbonated Apatite (HCA), that is to say, a hydroxyapatite which is similar to that naturally present in a bone tissue.
This being the case, no conclusion has been drawn from all these hypotheses formulated in documentation although titanium implants are being increasingly used and porous titanium implants whose characteristics of porosity are very similar to those of the human bone have even recently appeared.
In the wording of a patent application filed in parallel with this one by the same filing company, there has been proposed a new method for processing the surface of a titanium implant by means of immersion in a bath of sodium hydroxide which modifies the layer of oxides naturally present on the titanium and which renders bioactive this metal which is naturally bioinert, which thus allows a strong chemical connection of the bone to the implant produced from such a metal and which consequently promotes the osteointegration of the implant.
The chemical and mechanical stability of the effects of this processing with sodium hydroxide is, however, uncertain.
An object of the present invention is therefore to overcome this possible disadvantage.